github link
Accession IconSRP115022

Nuclear receptor Nur77 limits the macrophage inflammatory response by reprogramming mitochondrial metabolism (RNA-seq)

Organism Icon Mus musculus
Sample Icon 6 Downloadable Samples
Technology Badge IconIllumina HiSeq 2500

Submitter Supplied Information

Description
Activation of macrophages by inflammatory stimuli leads to reprogramming of mitochondrial metabolism to support the production of pro-inflammatory cytokines. Hallmarks of this metabolic rewiring are downregulation of a-ketoglutarate formation via isocitrate dehydrogenase (IDH) and accumulation of glutamine-derived succinate, which enhances the inflammatory response via the activity of succinate dehydrogenase (SDH). Here, we identify the nuclear receptor Nur77 (Nr4a1) as a key regulator of the pro-inflammatory metabolic switch in macrophages. Nur77-deficient macrophages fail to downregulate IDH expression and accumulate higher levels of succinate and other downstream TCA cycle metabolites in response to an inflammatory stimulus. Consequently, these macrophages produce more nitric oxide and pro-inflammatory cytokines in an SDH-dependent manner. In vivo, bone marrow Nur77 deficiency exacerbates atherosclerosis development and leads to increased systemic succinate levels. In conclusion, Nur77 supports an anti-inflammatory metabolic state in macrophages that protects against chronic inflammatory diseases such as atherosclerosis. Overall design: Gene expression profiling by RNA-seq was performed in triplicate in RAW264.7 mouse macrophage stable cell lines with doxycycline-inducible overexpression of HA-tagged NUR77 or GFP as control.
PubMed ID
Total Samples
6
Submitter’s Institution
No associated institution

Samples

Show of 0 Total Samples
Filter
Add/Remove
Accession Code
Title
Cell line
Treatment
Subject
Processing Information
Additional Metadata
No rows found
Loading...